It is often difficult to determine the timing, evolution and extent of brain injury in infants due to the insensitivity of the neurological exam and of current bedside methods. The first year of life is a critical period in brain development, as abnormalities that can go undetected for months or even years may occur during this time. Delayed diagnosis of cerebral abnormalities leads to delayed intervention and may have a negative impact on outcome. To promptly detect neonatal brain injury, to understand normal developmental trajectories, to distinguish abnormal from normal trajectories, and to provide early assessment of the consequences of injury on brain development, a safe, bedside technique is needed to quantitatively and reliably monitor regional brain health and development. We believe we can achieve this goal by combining two optical noninvasive techniques. Frequency-domain near-infrared spectroscopy (FD-NIRS) provides bedside monitoring of regional cerebral blood volume and oxygenation, while diffuse correlation spectroscopy (DCS) measures regional cerebral blood velocity. The combination of the two techniques provides an estimate of cerebral oxygen metabolism. Our hypotheses are that the optical measure related to oxygen consumption will correlate best with clinical assessment and outcome of brain damage. In this proposal, we will advance the optical method to quantify baseline cerebral blood flow and oxygen consumption, validate these measurements against MRI measurements in animals and humans, and assess the accuracy of the method with Monte Carlo simulations on 3D segmented MRI heads. We will then perform longitudinal FD-NIRS and DCS measurements in healthy and sick infants during the first year of life. By comparing results in healthy and sick infants, we will be able to test our hypotheses that the optical measure of oxygen consumption can detect brain damage and its effect on brain development. Brain damage detection and stratification will be correlated with clinical diagnosis using MRI, EEG and neurological exams; normal and abnormal brain development trajectories will be correlated with the results of our behavioral and neuro-physiological development tests and, when available with clinical follow-up exams. The long-term objective of the proposed project is to establish FD-NIRS and DCS optical techniques as new standards for monitoring neonatal brain health and metabolic and hemodynamic development in the normal and diseased brain. This new measure could have an impact on neonatal care, prompt early intervention to prevent further damage, provide an estimate of the "window of opportunity" for treatment, help stratify neonates for therapeutic interventions, and become a tool for evaluating response to therapy. [unreadable] [unreadable] [unreadable]